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CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells

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Item Type:Article
Title:CD95 maintains stem cell-like and non-classical EMT programs in primary human glioblastoma cells
Creators Name:Drachsler, M. and Kleber, S. and Mateos, A. and Volk, K. and Mohr, N. and Chen, S. and Cirovic, B. and Tuettenberg, J. and Gieffers, C. and Sykora, J. and Wirtz, C.R. and Mueller, W. and Synowitz, M. and Martin-Villalba, A.
Abstract:Glioblastoma (GBM) is one of the most aggressive types of cancer with limited therapeutic options and unfavorable prognosis. Stemness and non-classical epithelial-to-mesenchymal transition (ncEMT) features underlie the switch from normal to neoplastic states as well as resistance of tumor clones to current therapies. Therefore, identification of ligand/receptor systems maintaining this privileged state is needed to devise efficient cancer therapies. In this study, we show that the expression of CD95 associates with stemness and EMT features in GBM tumors and cells and serves as a prognostic biomarker. CD95 expression increases in tumors and with tumor relapse as compared with non-tumor tissue. Recruitment of the activating PI3K subunit, p85, to CD95 death domain is required for maintenance of EMT-related transcripts. A combination of the current GBM therapy, temozolomide, with a CD95 inhibitor dramatically abrogates tumor sphere formation. This study molecularly dissects the role of CD95 in GBM cells and contributes the rational for CD95 inhibition as a GBM therapy.
Keywords:Alkylating Antineoplastic Agents, Brain Neoplasms, CD95 Antigens, Cellular Spheroids, Class Ia Phosphatidylinositol 3-Kinase, Dacarbazine, Drug Combinations, Drug Synergism, Epithelial-Mesenchymal Transition, Glioblastoma, Immunoglobulin G, Local Neoplasm Recurrence, Messenger RNA, Neoplastic Gene Expression Regulation, Neoplastic Stem Cells, Primary Cell Culture, Prognosis, Recombinant Fusion Proteins, Signal Transduction, Survival Analysis
Source:Cell Death & Disease
Publisher:Nature Publishing Group
Page Range:e2209
Date:28 April 2016
Additional Information:Erratum in: Cell Death Dis 11(7): 558.
Official Publication:https://doi.org/10.1038/cddis.2016.102
PubMed:View item in PubMed

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